Bet v 1, the major birch pollen allergen, conjugated to crystalline bacterial cell surface proteins, expands allergen-specific T cells of the Th1/Th0 phenotype in vitro by induction of IL-12.
Modulation of allergic immune responses by using adequate adjuvants is a promising concept for future immunotherapy of type I hypersensitivity. In the present study, recombinant Bet v 1 (rBet v 1, the major birch pollen allergen) was conjugated to cross-linked crystalline surface layer proteins (SL) derived from Gram-positive eubacteria. T cell lines (TCL) and clones (TCC) were established from peripheral blood of birch pollen-allergic patients. TCL and TCC were induced either using rBet v 1 alone or rBet v 1/SL conjugates (rBet v 1/SL) as initial antigen stimulus. Cytokine production after re-stimulation with rBet v 1 was investigated. TCL initiated with rBet v 1/SL showed significantly increased IFN-gamma production as compared to rBet v 1 -selected TCL. TCC were established from TCL of five patients. As expected, the majority of CD4+ TCC induced by rBet v 1 (55%) displayed a Th2-like pattern of cytokine production. However, only 21% of Bet v 1-specific TCC isolated from TCL established with the Bet v 1/SL revealed this phenotype. The majority of SL-specific TCC (80%) belonged to the Th1 phenotype. In cultures of peripheral blood mononuclear cells, both, SL and Bet v 1/SL (but not rBet v 1) stimulated the production of high levels of IL-12, a pivotal mediator of Th1 responses. Moreover, stimulation of rBet v 1-induced TCC with rBet v 1/SL led to an increased IFN-gamma production. This effect could be reversed by neutralizing anti-IL-12 mAb. Together these results indicate an adjuvant effect of SL mediated by IL-12. Our results indicate that bacterial components, such as SL, displaying adjuvant effects may be suitable for immunotherapeutical vaccines for type I allergy.
Jahn-Schmid
B
B
Zentrum für Ultrastrukturforschung und Ludwig Boltzmann-Institut für Molekulare Nanotechnologie, Universität für Bodenkultur, Wein, Austria.
Siemann
U
U
Zenker
A
A
Bohle
B
B
Messner
P
P
Unger
F M
FM
Sleytr
U B
UB
Scheiner
O
O
Kraft
D
D
Ebner
C
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D010641:Phenotype; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D011058:Pollen / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; D001426:Bacterial Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D018664:Interleukin-12; D007371:Interferon-gamma